Gene expression signatures of radiation response are specific, durable and accurate in mice and humans.

BACKGROUND: Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. METHODS AND FINDINGS: We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively. CONCLUSIONS: We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.

Application description and policy model in collaborative environment for sharing of information on epidemiological and clinical research data sets.

BACKGROUND: Sharing of epidemiological and clinical data sets among researchers is poor at best, in detriment of science and community at large. The purpose of this paper is therefore to (1) describe a novel Web application designed to share information on study data sets focusing on epidemiological clinical research in a collaborative environment and (2) create a policy model placing this collaborative environment into the current scientific social context. METHODOLOGY: The Database of Databases application was developed based on feedback from epidemiologists and clinical researchers requiring a Web-based platform that would allow for sharing of information about epidemiological and clinical study data sets in a collaborative environment. This platform should ensure that researchers can modify the information. A Model-based predictions of number of publications and funding resulting from combinations of different policy implementation strategies (for metadata and data sharing) were generated using System Dynamics modeling. PRINCIPAL FINDINGS: The application allows researchers to easily upload information about clinical study data sets, which is searchable and modifiable by other users in a wiki environment. All modifications are filtered by the database principal investigator in order to maintain quality control. The application has been extensively tested and currently contains 130 clinical study data sets from the United States, Australia, China and Singapore. Model results indicated that any policy implementation would be better than the current strategy, that metadata sharing is better than data-sharing, and that combined policies achieve the best results in terms of publications. CONCLUSIONS: Based on our empirical observations and resulting model, the social network environment surrounding the application can assist epidemiologists and clinical researchers contribute and search for metadata in a collaborative environment, thus potentially facilitating collaboration efforts among research communities distributed around the globe.

What leads Indians to participate in clinical trials? A meta-analysis of qualitative studies.

BACKGROUND: With the globalization of clinical trials, large developing nations have substantially increased their participation in multi-site studies. This participation has raised ethical concerns, among them the fear that local customs, habits and culture are not respected while asking potential participants to take part in study. This knowledge gap is particularly noticeable among Indian subjects, since despite the large number of participants, little is known regarding what factors affect their willingness to participate in clinical trials. METHODS: We conducted a meta-analysis of all studies evaluating the factors and barriers, from the perspective of potential Indian participants, contributing to their participation in clinical trials. We searched both international as well as Indian-specific bibliographic databases, including Pubmed, Cochrane, Openjgate, MedInd, Scirus and Medknow, also performing hand searches and communicating with authors to obtain additional references. We enrolled studies dealing exclusively with the participation of Indians in clinical trials. Data extraction was conducted by three researchers, with disagreement being resolved by consensus. RESULTS: Six qualitative studies and one survey were found evaluating the main themes affecting the participation of Indian subjects. Themes included Personal health benefits, Altruism, Trust in physicians, Source of extra income, Detailed knowledge, Methods for motivating participants as factors favoring, while Mistrust on trial organizations, Concerns about efficacy and safety of trials, Psychological reasons, Trial burden, Loss of confidentiality, Dependency issues, Language as the barriers. CONCLUSION: We identified factors that facilitated and barriers that have negative implications on trial participation decisions in Indian subjects. Due consideration and weightage should be assigned to these factors while planning future trials in India.

The development and psychometric properties of the HIV and Abuse Related Shame Inventory (HARSI).

Shame has been shown to predict sexual HIV transmission risk behavior, medication non-adherence, symptomatic HIV or AIDS, and symptoms of depression and PTSD. However, there remains a dearth of tools to measure the specific constructs of HIV-related and sexual abuse-related shame. To ameliorate this gap, we present a 31-item measure that assesses HIV and sexual abuse-related shame, and the impact of shame on HIV-related health behaviors. A diverse sample of 271 HIV-positive men and women who were sexually abused as children completed the HIV and Abuse Related Shame Inventory (HARSI) among other measures. An exploratory factor analysis supported the retention of three-factors, explaining 56.7% of the sample variance. These internally consistent factors showed good test-retest reliability, and sound convergent and divergent validity using eight well-established HIV specific and general psychosocial criterion measures. Unlike stigma or discrimination, shame is potentially alterable through individually-focused interventions, making the measurement of shame clinically meaningful.

Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders.

The centrality of event scale: a measure of integrating a trauma into one's identity and its relation to post-traumatic stress disorder symptoms.

We introduce a new scale that measures how central an event is to a person's identity and life story. For the most stressful or traumatic event in a person's life, the full 20-item Centrality of Event Scale (CES) and the short 7-item scale are reliable (alpha's of .94 and .88, respectively) in a sample of 707 undergraduates. The scale correlates .38 with PTSD symptom severity and .23 with depression. The present findings are discussed in relation to previous work on individual differences related to PTSD symptoms. Possible connections between the CES and measures of maladaptive attributions and rumination are considered along with suggestions for future research.

Cost-effectiveness analysis of the diagnosis of meniscus tears.

BACKGROUND: Diagnostic imaging represents the fastest growing segment of costs in the US health system. This study investigated the cost-effectiveness of alternative diagnostic approaches to meniscus tears of the knee, a highly prevalent disease that traditionally relies on MRI as part of the diagnostic strategy. PURPOSE: To identify the most efficient strategy for the diagnosis of meniscus tears. STUDY DESIGN: Economic and decision analysis; Level of evidence, 1. METHODS: A simple-decision model run as a cost-utility analysis was constructed to assess the value added by MRI in various combinations with patient history and physical examination (H&P). The model examined traumatic and degenerative tears in 2 distinct settings: primary care and orthopaedic sports medicine clinic. Strategies were compared using the incremental cost-effectiveness ratio (ICER). RESULTS: In both practice settings, H&P alone was widely preferred for degenerative meniscus tears. Performing MRI to confirm a positive H&P was preferred for traumatic tears in both practice settings, with a willingness to pay of less than US$50,000 per quality-adjusted life-year. Performing an MRI for all patients was not preferred in any reasonable clinical scenario. The prevalence of a meniscus tear in a clinician's patient population was influential. For traumatic tears, MRI to confirm a positive H&P was preferred when prevalence was less than 46.7%, with H&P preferred above that. For degenerative tears, H&P was preferred until the prevalence reaches 74.2%, and then MRI to confirm a negative was the preferred strategy. In both settings, MRI to confirm positive physical examination led to more than a 10-fold lower rate of unnecessary surgeries than did any other strategy, while MRI to confirm negative physical examination led to a 2.08 and 2.26 higher rate than H&P alone in primary care and orthopaedic clinics, respectively. CONCLUSION: For all practitioners, H&P is the preferred strategy for the suspected degenerative meniscus tear. An MRI to confirm a positive H&P is preferred for traumatic tears for all practitioners. Consideration should be given to implementing alternative diagnostic strategies as well as enhancing provider education in physical examination skills to improve the reliability of H&P as a diagnostic test. CLINICAL RELEVANCE: Alternative diagnostic strategies that do not include the use of MRI may result in decreased health care costs without harm to the patient and could possibly reduce unnecessary procedures.

Sensitive and precise quantification of insulin-like mRNA expression in Caenorhabditis elegans.

Insulin-like signaling regulates developmental arrest, stress resistance and lifespan in the nematode Caenorhabditis elegans. However, the genome encodes 40 insulin-like peptides, and the regulation and function of individual peptides is largely uncharacterized. We used the nCounter platform to measure mRNA expression of all 40 insulin-like peptides as well as the insulin-like receptor daf-2, its transcriptional effector daf-16, and the daf-16 target gene sod-3. We validated the platform using 53 RNA samples previously characterized by high density oligonucleotide microarray analysis. For this set of genes and the standard nCounter protocol, sensitivity and precision were comparable between the two platforms. We optimized conditions of the nCounter assay by varying the mass of total RNA used for hybridization, thereby increasing sensitivity up to 50-fold and reducing the median coefficient of variation as much as 4-fold. We used deletion mutants to demonstrate specificity of the assay, and we used optimized conditions to assay insulin-like gene expression throughout the C. elegans life cycle. We detected expression for nearly all insulin-like genes and find that they are expressed in a variety of distinct patterns suggesting complexity of regulation and specificity of function. We identified insulin-like genes that are specifically expressed during developmental arrest, larval development, adulthood and embryogenesis. These results demonstrate that the nCounter platform provides a powerful approach to analyzing insulin-like gene expression dynamics, and they suggest hypotheses about the function of individual insulin-like genes.

Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.

Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

Sun glint estimation in marine satellite images: a comparison of results from calculation and radiative transfer modeling

The intensity and location of Sun glint in two Medium Resolution Imaging Spectrometer (MERIS) images was modeled using a radiative transfer model that includes elevation features as well as the slope of the sea surface. The results are compared to estimates made using glint flagging and correction approaches used within standard atmospheric correction processing code. The model estimate gives a glint pattern with a similar width but lower peak level than any current method, or than that estimated by a radiative transfer model with surfaces that include slope but not height. The MERIS third reprocessing recently adopted a new slope statistics model for Sun glint correction; the results show that this model is an outlier with respect to both the elevation model and other slope statistics models and we recommend that its adoption should be reviewed.

Monitoring changes in phytoplankton abundance and composition in the Northwest Atlantic: a comparison of results obtained by Continuous Plankton Recorder sampling and colour satellite imagery

Phytoplankton abundance in the NW Atlantic was measured by continuous plankton recorder (CPR) sampling along tracks between Iceland and the western Scotian Shelf from 1998 to 2006, when sea-surface chlorophyll (SSChl) measurements were also being made by ocean colour satellite imagery using the SeaWiFS sensor. Seasonal and inter-annual changes in phytoplankton abundance were examined using data collected by both techniques, averaged over each of four shelf regions and four deep ocean regions. CPR sampling had gaps (missing months) in all regions and in the four deep ocean regions satellite observations were too sparse between November and February to be of use. Average seasonal cycles of SSChl were similar to those of total diatom abundance in seven regions, to those of the phytoplankton colour index in six regions, but were not similar to those of total dinoflagellate abundance anywhere. Large inter-annual changes in spring bloom dynamics were captured by both samplers in shelf regions. Changes in annual (or 8 months) averages of SSChl did not generally follow those of the CPR indices within regions and multi-year averages of SSChl, and the three CPR indices were generally higher in shelf than in deep ocean regions. Remote sensing and CPR sampling provide complementary ways of monitoring phytoplankton in the ocean: the former has superior temporal and spatial coverage and temporal resolution, and the latter provides better taxonomic information.

LibQUAL+ Survey 2004 @ Queen's University Library : analysis of results

Queen's University Library was one of 202 libraries, including 57 members of the Association of Research Libraries (ARL), to survey its users in spring 2004 using the LibQUAL+ survey instrument. LibQUAL+ was designed by ARL to assist libraries in assessing the quality of their services and identifying areas for improvement. # Overall: Queen's scored higher than the average for all ARL participants and 1st among the 2004 Canadian participants. This relatively high rating is due to very high scores in the dimensions of Library as Place and Affect of Service. However, there is considerable need for improvement in the area of Information Control where Queen's rated well below the ARL average. # Affect of Service: Queen's strong overall ratings are supported by the many respondent comments praising customer service throughout the system. The ratings and survey comments indicate greatest appreciation by faculty and more experienced students (e.g. graduate students) for the instruction and on-site services provided by the libraries. The ratings also indicate that undergraduates, growing up with the web, want and expected to be able to access library resources independently and do not value these services as highly. The comments also indicated some specific areas for improvement throughout the library system. # Library as Place : All Queen's libraries except for Law ranked well above the ARL and Canadian averages. Overall, Library as Place ranked lowest in importance among the service dimensions for all ARL participants including Queen's. Comparative analysis of LibQUAL results since the survey began shows a decline in “desired” ratings for Library as Place. However, undergraduates continue to give strong "desired" ratings to certain aspects of Library as Place and a relatively high rating for "minimum expected" service. The comments from Queen's survey respondents and ARL's analyses of focus groups indicate that undergraduates value the library much more as a place to study and work with peers rather than for its on-site resources and services. # Information Control: This is the area in greatest need of attention. While it ranked highest in importance for all user groups by a wide margin, Queen's performed poorly in this category. Overall, Queen's ranked far below both the ARL average and the top three Canadian scores. However, the major dissatisfaction was concentrated in the humanities/social sciences (Stauffer primary users) and the health sciences (Bracken primary users) where the overall rating of perceived service quality ranked below the minimum expected service rating. Primary users of the Education, Engineering/Science and Law libraries rated this service dimension higher than the ARL average. The great success of the Canadian National Site License Program (CNSLP) is reflected in the high overall rating generated by Engineering/Science Library users. The low ratings from the humanities and social sciences are supported by respondents' comments and are generally consistent with other ARL participants.

LibQUAL+ Survey 2007 at Queen’s University Library: Analysis of Results

Analysis of 2007 LibQUAL+ results from the survey conducted by Queen's University in February 2007.